Case Presentation
A 22-year-old male presented to the emergency department with complaints of sudden-onset weakness in both legs that progressed to involve his arms over two hours. He was unable to stand or lift objects. The weakness was flaccid and painless, with no sensory disturbances, bowel or bladder involvement, or preceding fever or trauma. He mentioned a similar episode six months ago which resolved on its own. This time, the episode followed a heavy carbohydrate-rich meal after a strenuous workout.
His family history revealed that his older brother had experienced similar episodes during adolescence. On examination, the patient was fully conscious and oriented. Motor examination showed 2/5 power in all four limbs with diminished deep tendon reflexes. Sensory and cranial nerve exams were normal.
Investigations revealed:
- Serum potassium: 2.2 mEq/L
- Serum calcium and magnesium: Normal
- ECG: Flattened T waves and prominent U waves
- Thyroid function tests: Within normal range
The patient was diagnosed with Hypokalemic Periodic Paralysis (HPP) and was managed with intravenous potassium replacement. Within 12 hours, his strength improved significantly.
Introduction
Hypokalemic Periodic Paralysis (HPP) is a rare, inherited muscle disorder characterized by recurrent episodes of muscle weakness associated with low serum potassium levels. These episodes are transient but can be severe and potentially life-threatening if not promptly recognized and treated.
It typically affects young males and is most commonly inherited in an autosomal dominant fashion, although sporadic cases do occur.
Etiology and Pathophysiology
HPP is most often caused by mutations in genes encoding ion channels in skeletal muscles:
- CACNA1S gene: Encodes the α1-subunit of the dihydropyridine-sensitive calcium channel (more common).
- SCN4A gene: Encodes the skeletal muscle sodium channel.
These mutations result in abnormal membrane excitability. During triggers such as high carbohydrate meals, rest after exercise, or stress, insulin drives potassium into cells, worsening hypokalemia and reducing muscle excitability. The result is transient flaccid paralysis.
Precipitating Factors
- High-carbohydrate meals
- Rest after vigorous exercise
- Stress or infection
- Cold exposure
- Certain medications (e.g., insulin, beta-agonists)
Clinical Features
- Onset usually in adolescence or early adulthood
- Sudden, symmetric, flaccid muscle weakness (legs > arms)
- No sensory loss or altered mental status
- Episodes last a few hours to a day
- Normal muscle strength between attacks
- Reflexes may be decreased during attacks
Note: Respiratory and facial muscles are rarely involved, but severe cases can affect breathing or cardiac rhythm due to extreme hypokalemia.
Differential Diagnosis
- Thyrotoxic Periodic Paralysis – similar symptoms but associated with hyperthyroidism (more common in Asian males).
- Guillain-Barré Syndrome – ascending weakness, often with sensory symptoms and absent reflexes.
- Myasthenia Gravis – fluctuating weakness, especially facial and ocular muscles.
- Familial periodic paralysis with normokalemia or hyperkalemia
Diagnosis
- Clinical history of episodic weakness, especially after triggers
- Low serum potassium during attacks
- ECG changes (U waves, flattened T waves)
- Genetic testing to confirm mutations
- Normal thyroid profile helps rule out thyrotoxic periodic paralysis
Management
Acute Attack:
- Potassium supplementation (oral or IV depending on severity)
- Monitor ECG for arrhythmias
- Avoid overcorrection to prevent rebound hyperkalemia
Long-term Management:
- Lifestyle modifications: Avoid triggers, balanced diet
- Acetazolamide or dichlorphenamide (carbonic anhydrase inhibitors): Prevent attacks by altering ion transport
- Genetic counseling for affected families
Prognosis
With proper recognition and management, the prognosis is generally favorable. However, recurrent untreated episodes can lead to progressive, fixed muscle weakness over time due to muscle damage.
Conclusion
Hypokalemic Periodic Paralysis is a rare but important cause of acute, reversible muscle weakness in young individuals. Prompt diagnosis, correction of hypokalemia, and preventive strategies can significantly improve quality of life and prevent complications. Clinicians should maintain a high index of suspicion, especially when weakness follows exercise or carbohydrate-rich meals in a young male with a family history of similar symptoms.